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1.
Chem Commun (Camb) ; 59(88): 13219-13222, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37855171

ABSTRACT

In this investigation, a lithium-free cathode material, Na0.7MnO2.05-Na0.91MnO2, was synthesized by the solid phase method. The intercalation mechanism and partial phase transformation mechanism of NMO600 were clarified by in situ X-ray diffraction and impedance. The design of the heterostructure is favourable for improving the lithium ion storage of NMO600, which can deliver a discharge capacity of 83.12 mA h g-1 at 1 A g-1 and keep 61.71 mA h g-1 after 700 cycles.

2.
Eur J Med Chem ; 178: 329-340, 2019 Sep 15.
Article in English | MEDLINE | ID: mdl-31200235

ABSTRACT

A novel series of 6-substituted pyrrolo[2,3-d]pyrimidines with reversed amide moieties from the lead compound 1a were designed and synthesized as nonclassical antifolates and as potential antitumor agents. Target compounds 1-9 were successfully obtained through two sequential condensation reactions from the key intermediate 2-amino-6-(2-aminoethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one. In preliminary antiproliferation assay, all compounds demonstrated submicromolar to nanomolar inhibitory effects against KB tumor cells, whereas compounds 1-3 also exhibited nanomolar antiproliferative activities toward SW620 and A549 cells. In particular, compounds 1-3 were significantly more potent than the positive control methotrexate (MTX) and pemetrexed (PMX) to A549 cells. The growth inhibition induced cell cycle arrest at G1-phase with S-phase suppression. Along with the results of nucleoside protection assays, inhibition assays of dihydrofolate reductase (DHFR) clearly elucidated that the intracellular target of the designed compounds was DHFR. Molecular modeling studies suggested two binding modes of the target compounds with DHFR.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Folic Acid Antagonists/pharmacology , Folic Acid/metabolism , Pyrimidines/pharmacology , Pyrroles/pharmacology , Tetrahydrofolate Dehydrogenase/metabolism , A549 Cells , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Folic Acid Antagonists/chemical synthesis , Folic Acid Antagonists/chemistry , Humans , KB Cells , Molecular Structure , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Pyrroles/chemical synthesis , Pyrroles/chemistry , Structure-Activity Relationship
3.
Eur J Med Chem ; 139: 531-541, 2017 Oct 20.
Article in English | MEDLINE | ID: mdl-28830032

ABSTRACT

A novel series of 6-substituted benzoyl and non-benzoyl straight chain pyrrolo[2,3-d]pyrimidines were designed and synthesized as potential antitumor agents targeting both thymidylate and purine nucleotide biosynthesis. Starting from the key intermediate 2-amino-4-oxo-pyrrolo[2,3-d]pyrimidin-6-yl-acetic acid, target compounds 1-6 were successfully obtained through two sequential condensation and saponification reactions in decent yield. The newly synthesized compounds showed antiproliferative potencies against a panel of tumor cell lines including KB, SW620 and MCF7. In particular, most compounds of this series exhibited nanomolar to subnanomolar inhibitory activities toward KB tumor cells, significantly more potent than the positive control methotrexate (MTX) and pemetrexed (PMX). Along with the results of nucleoside protection assays, molecular modeling studies suggested that the antitumor activity of compound 6 could be attributed to multitargeted inhibition of folate-dependent enzymes thymidylate synthase (TS), glycinamide ribonucleotide formyltransferase (GARFTase) and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFTase). Growth inhibition by compound 6 also induced distinct early apoptosis and cell cycle arrest at S-phase, which resulted in cell death.


Subject(s)
Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Phosphoribosylaminoimidazolecarboxamide Formyltransferase/antagonists & inhibitors , Phosphoribosylglycinamide Formyltransferase/antagonists & inhibitors , Pyrimidines/pharmacology , Pyrroles/pharmacology , Thymidylate Synthase/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Models, Molecular , Molecular Structure , Phosphoribosylaminoimidazolecarboxamide Formyltransferase/metabolism , Phosphoribosylglycinamide Formyltransferase/metabolism , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Pyrroles/chemical synthesis , Pyrroles/chemistry , Structure-Activity Relationship , Thymidylate Synthase/metabolism
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